The goal of this proposal is to assess abnormalities in brain structure and function in patients diagnosed with type I bipolar disorder (history of manic episode) who are currently euthymic. Patients and healthy volunteers will undergo structural and functional magnetic resonance imaging. Functional imaging will take place during the performance of a neuropsychological task known to activate ventral prefrontal cortex and amygdala, known components of the emotion regulatory system. Advanced surface based processing algorithms will be used on high resolution structural images to measure gray matter thickness in frontal cortex and other brain regions. A correlation analysis will then be used to assess, at every point along the cortex, the relationship between cortical thickness and fMR signal intensity. Because ventral frontal regions of cortex send direct inhibitory projections to the amygdala, the relationship between ventral prefrontal cortical thinning and the response level of the amygdala will also be examined. These studies represent the first attempt at characterizing the thickness of the frontal cortex in bipolar disorder and how structural abnormalities in this region impact functioning of fronto-limbic mood regulatory circuits. Results from the proposed experiments will help to advance our understanding of the pathophysiology of bipolar disorder and identify phenotypic brain abnormalities that predispose an individual to extreme liabilities in mood. Future studies that examine the emergence and progression of these brain abnormalities and the associated impact of medications and treatments will serve to have profound prognostic consequences for patients.